The World Health Organisation (WHO) confirmed in August that a baby was partially paralysed by the type 2 polio virus, the first such case in the territory in 25 years.
The campaign began on Sunday in areas of central Gaza, and will move to other areas in coming days.
Children in — Tedros Adhanom Ghebreyesus (@DrTedros) #Gaza are receiving much-needed #polio vaccines today. Ultimately, the best vaccine for these children is peace. pic.twitter.com/yD1AIoXvpFSeptember 1, 2024
Fighting will pause for at least eight hours on three consecutive days.
The WHO said the pauses will likely need to extend to a fourth day and the first round of vaccinations will take just under two weeks.
"This is the first few hours of the first phase of a massive campaign, one of the most complex in the world," said Juliette Touma, communications director of UNRWA, the UN Palestinian refugee agency.
"Today is test time for parties to the conflict to respect these area pauses to allow the UNRWA teams and other medical workers to reach children with these very precious two drops.
"It's a race against time," Touma told Reuters.
Israel and Hamas, who have so far failed to conclude a deal that would end the war, said they would co-operate to allow the campaign to succeed.
Israel and Hamas have vowed to co-operate to allow polio vaccinations in Gaza to proceed. (AP PHOTO)
WHO officials say at least 90 per cent of the children need to be vaccinated twice with four weeks between doses for the campaign to succeed, but it faces huge challenges in Gaza, which has been largely destroyed by the war.
"Children continue to be exposed - it knows no borders, checkpoints or lines of fighting," Touma said.
"Every child must be vaccinated in Gaza and Israel to curb the risks of this vicious disease spreading."
The vaccinations began as Israeli forces continued to battle Hamas-led militants in several areas across the Palestinian enclave.
The war was triggered after Hamas militants stormed into southern Israel on October 7, killing 1200 people and taking more than 250 hostages by Israeli tallies.
Since then, at least 40,691 Palestinians have been killed and 94,060 injured in Gaza, the enclave's health ministry says.